Project Summary Scientists and laypeople have long been fascinated by the senses. Aristotle distinguished four of them, each linked with one of the four elements ? vision with water, sound with air, smell with fire, and touch with earth. Since that time we have become aware of many more, including those involving position or pain. Now, research across a range of disciplines has revealed that sensory perception is capable of modulating many aspects of physiology and health. Indeed, evidence from work in the nematode, Caenorhabditis elegans, and from our work in the fruit fly, Drosophila melanogaster, has established that aging is strongly modulated by sensory systems and that this modulation is evolutionarily conserved. Apfeld and Kenyon used the nematode model to show that suppression of sensory input could extend lifespan. Subsequent work from our lab and others has extended these results to Drosophila and revealed an increasingly nuanced relationship between sensory perception and aging. For example, some sensory neurons enhance longevity while others suppress it. In this renewal, we continue our research to focus on the dissection of interpretive circuits in the brain that process and interpret of sensory experiences in the brain. Having identified specific olfactory and gustatory manipulations that modulate aging, we propose here to build on the foundational results described above and probe deeper to identify specific signaling molecules and control regions in the brain that orchestrate sensory modulation of aging. Recent discoveries from our laboratory and others have revealed cause and effect relationships linking the neurobiology of perception to complex behavioral outputs; thus making Drosophila arguably the most relevant, powerful, and flexible model system to dissect the mechanisms underlying central control of aging and whole-organism physiology. We believe that harnessing the neurobiology of simple model systems to study the biological impact of sensory systems will yield insights into the broad influence of sensory perception across taxa. In support of this view, there is evidence to suggest that human sensory perception can modulate health and aging in response to social and nutritional cues in ways that we do not yet understand. The human demographic and epidemiological literatures are filled with associations linking emotions, cognitive experience, and subjective assessments of ?well-being? with health and lifespan. The presumed importance of these factors belies a near complete lack of understanding of the causality of the relationships. Herein we propose a mechanistic framework for studying them.